Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
Open accessAbstract
The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Natural cancer immunosurveillance can be negatively impacted by gut commensals through TLR5- and IL-6-dependent inflammation.
“In contrast, the natural immunosurveillance of cancers can be negatively impacted by gut commensals through TLR5- and IL-6-dependent inflammation.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [36]
The gut microbiome has multiple effects on tumor biology, including transformation, progression, and response to anticancer therapies including immunotherapy.
“The gut microbiome has been shown to have multiple effects on tumor biology, such as the transformation process, tumor progression, and the response to anticancer therapies including immunotherapy (21-29).”
From The human tumor microbiome is composed of tumor type–specific intracellular bacteria (2020) · cites this paper as [29]
The interaction resulted in IL-6-dependent mobilization of MDSCs and subsequently more γδT cells producing immunosuppressive galectin-1, followed by impaired antitumor response and accelerated malignant progression.
“The interaction resulted in IL-6-dependent mobilization of MDSCs and subsequently more γδT cells producing immunosuppressive galectin-1, followed by impaired antitumor response and accelerated malignant progression [60] (Fig. 2).”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [60]
Bacterial flagellin stimulated pro-tumoral inflammation through TLR5 signaling.
“The notion was further supported by another study showing bacterial flagellin stimulated pro-tumoral inflammation through TLR5 signaling [60].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [60]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340 · see citing works
Commensal Bacteria Control Cancer Response to Therapy by Modulating the Tumor Microenvironment
Iida, N., Dzutsev, A., Stewart, C. A., Smith, L., Bouladoux, N., Weingarten, R. A., Molina, D. A., Salcedo, R., Back, T., Cramer, S., et al. (2013) · Science · doi:10.1126/science.1240527 · Cited by 2,251 · see citing works
The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide
Viaud, S., Saccheri, F., Mignot, G., Yamazaki, T., Daillère, R., Hannani, D., Enot, D. P., Pfirschke, C., Engblom, C., Pittet, M. J., et al. (2013) · Science · doi:10.1126/science.1240537 · Cited by 2,050 · see citing works
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,877 · see citing works
Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity
Clarke, T. B., Davis, K. M., Lysenko, E. S., Zhou, A. Y., Yu, Y., & Weiser, J. N. (2010) · Nature Medicine · doi:10.1038/nm.2087 · Cited by 1,154 · see citing works
Jonkers, J., Meuwissen, R. L. J., van der Gulden, H. M. L., Peterse, H. L., van der Valk, M., & Berns, A. J. M. (2001) · Nature Genetics · doi:10.1038/ng747 · Cited by 1,053 · see citing works
Commensal bacteria calibrate the activation threshold of innate antiviral immunity
Abt, M. C., Osborne, L. C., Monticelli, L. A., Doering, T. A., Alenghat, T., Sonnenberg, G. F., Paley, M. A., Antenus, M., Williams, K. L., Erikson, J., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.04.011 · Cited by 993 · see citing works
IL-17 can promote tumor growth through an IL-6–Stat3 signaling pathway
Wang, L., Yi, T., Kortylewski, M., Pardoll, D. M., Zeng, D., & Yu, H. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090207 · Cited by 839 · see citing works
Kryczek, I., Banerjee, M., Cheng, P. J., Vatan, L., Szeliga, W., Wei, S., Huang, E. H., Finlayson, E. V. A., Simeone, D. M., Welling, T. H., et al. (2009) · Blood · doi:10.1182/blood-2009-03-208249 · Cited by 814 · see citing works
Toscano, M. A., Bianco, G. A., Ilarregui, J. M., Croci, D. O., Correale, J., Hernandez, J. D., Zwirner, N. W., Poirier, F., Riley, E. M., Baum, L. G., et al. (2007) · Nature Immunology · doi:10.1038/ni1482 · Cited by 653 · see citing works
Self-citationHawn, T. R., Verbon, A., Lettinga, K. D., Zhao, L. P., Li, S. S., Laws, R. J., Skerrett, S. J., Beutler, B., Schroeder, L. A., Nachman, A., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20031220 · Cited by 608 · see citing works
Rubinstein, N., Alvarez, M. J., Zwirner, N. W., Toscano, M. A., Ilarregui, J. M., Bravo, A., Mordoh, J., Fainboim, L., Podhajcer, O. L., & Rabinovich, G. A. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00024-8 · Cited by 529 · see citing works
Self-citationConejo-Garcia, J. R., Benencia, F., Courreges, M. C., Kang, E. H., Mohamed-Hadley, A. A., Buckanovich, R. J., Holtz, D. O., Jenkins, A., Na, H., Zhang, L., et al. (2004) · Nature Medicine · doi:10.1038/nm1097 · Cited by 438 · see citing works
Self-citationPeng, G., Wang, H. Y., Peng, W., Kiniwa, Y., Seo, K. H., & Wang, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.020 · Cited by 408 · see citing works
Casanova, J., Abel, L., & Quintana‐Murci, L. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101335 · Cited by 369 · see citing works
Regulatory Circuits Mediated by Lectin-Glycan Interactions in Autoimmunity and Cancer
Rabinovich, G. A., & Croci, D. O. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.004 · Cited by 338 · see citing works
Self-citationOvarian cancer progression is controlled by phenotypic changes in dendritic cells
Scarlett, U. K., Rutkowski, M. R., Rauwerdink, A. M., Fields, J. L., Escovar-Fadul, X., Baird, J. R., Cubillos‐Ruiz, J. R., Jacobs, A., Gonzalez, J. L., Weaver, J. B., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111413 · Cited by 314 · see citing works
Self-citationToll-like receptor polymorphisms and susceptibility to human disease
Misch, E. A., & Hawn, T. R. (2008) · Clinical Science · doi:10.1042/cs20070214 · Cited by 263 · see citing works
Dalotto‐Moreno, T., Croci, D. O., Cerliani, J. P., Allo, V. C. M., Dergan‐Dylon, S., Méndez‐Huergo, S. P., Stupirski, J. C., Mazal, D., Osinaga, E., Toscano, M. A., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2418 · Cited by 262 · see citing works
Self-citationAdenosinergic Regulation of the Expansion and Immunosuppressive Activity of CD11b+Gr1+ Cells
Ryzhov, S. V., Novitskiy, S. V., Goldstein, A. E., Biktasova, A., Blackburn, M. R., Biaggioni, I., Dikov, M. M., & Feoktistov, I. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101225 · Cited by 261 · see citing works
Toll-Like Receptor Polymorphisms and Susceptibility to Urinary Tract Infections in Adult Women
Hawn, T. R., Scholes, D., Li, S. S., Wang, H., Yang, Y., Roberts, P. L., Stapleton, A. E., Janer, M., Aderem, A. A., Stamm, W. E., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005990 · Cited by 209 · see citing works
Cubillos‐Ruiz, J. R., Engle, X. A., Scarlett, U. K., Martinez, D. G., Barber, A. E., Elgueta, R., Wang, L., Nesbeth, Y. C., Durant, Y. G., Gewirtz, A. T., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37716 · Cited by 208 · see citing works
Self-citationPrevalence of CARD15/NOD2 Mutations in Caucasian Healthy People
Hugot, J., Zaccaria, I., Cavanaugh, J. A., Yang, H., Vermeire, S., Lappalainen, M., Schreiber, S., Annese, V., Jewell, D. P., Fowler, E. V., et al. (2007) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01149.x · Cited by 200 · see citing works
Gewirtz, A. T., Vijay–Kumar, M., Brant, S. R., Duerr, R. H., Nicolae, D. L., & Cho, J. H. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00544.2005 · Cited by 197 · see citing works
Sampath, V., Garland, J. S., Le, M., Patel, A. L., Konduri, G. G., Cohen, J. D., Simpson, P. M., & Hines, R. N. (2011) · Pediatric Pulmonology · doi:10.1002/ppul.21568 · Cited by 44 · see citing works
Rutkowski, M. R., Allegrezza, M. J., Svoronos, N., Tesone, A. J., Stephen, T. L., Perales‐Puchalt, A., Nguyen, J. M., Zhang, P. J., Fiering, S., Tchou, J. C., et al. (2014) · Journal of Visualized Experiments · doi:10.3791/51171 · Cited by 24 · see citing works
Self-citationRutkowski, M. R., Allegrezza, M. J., Svoronos, N., Tesone, A. J., Stephen, T. L., Perales‐Puchalt, A., Nguyen, J., Zhang, P. J., Fiering, S., Tchou, J. C., et al. (2014) · Journal of Visualized Experiments · doi:10.3791/51171-v · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
1 of the 28 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Hawn TR Verbon A Lettinga KD Zhao LP Li SS Laws RJ Skerrett SJ Beutler B Schroeder L Nachman A A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease J Exp Med 2003b 198 1563 1572 14623910 PMC2194120
- Scarlett UK Rutkowski MR Rauwerdink AM Fields J Escovar-Fadul X Baird J Cubillos-Ruiz JR Jacobs AC Gonzalez JL Weaver J Ovarian cancer progression is controlled by phenotypic changes in dendritic cells J Exp Med 2012b 209 495 506 22351930 PMC3302234
Cited by
Sorted by citations
The human tumor microbiome is composed of tumor type–specific intracellular bacteria
Nejman, D., Livyatan, I., Fuks, G., Gavert, N., Zwang, Y., Geller, L. T., Rotter-Maskowitz, A., Weiser, R., Mallel, G., Gigi, E., et al. (2020) · Science · doi:10.1126/science.aay9189 · Cited by 2,464 · see citing works
Pushalkar, S., Hundeyin, M., Daley, D., Zambirinis, C. P., Kurz, E., Mishra, A., Mohan, N., Aykut, B., Usyk, M., Torres, L. E., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1134 · Cited by 1,400 · see citing works
Characteristics and Significance of the Pre-metastatic Niche
Liu, Y., & Cao, X. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.011 · Cited by 1,287 · see citing works
Pitt, J. M., Vétizou, M., Daillère, R., Roberti, M. P., Yamazaki, T., Routy, B., Lepage, P., Boneca, I. G., Chamaillard, M., Kroemer, G., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.06.001 · Cited by 1,040 · see citing works
Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation
Iyengar, N. M., Gucalp, A., Dannenberg, A. J., & Hudis, C. A. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.4283 · Cited by 1,004 · see citing works
Microbiota: a key orchestrator of cancer therapy
Roy, S., & Trinchieri, G. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.13 · Cited by 883 · see citing works
Daillère, R., Vétizou, M., Waldschmitt, N., Yamazaki, T., Isnard, C., Poirier-Colame, V., Duong, C. P. M., Flament, C., Lepage, P., Roberti, M. P., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.09.009 · Cited by 897 · see citing works
The Intestinal Microbiota in Colorectal Cancer.
Tilg, H., Adolph, T. E., Gerner, R. R., & Moschen, A. R. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.004 · Cited by 777 · see citing works
The role of the microbiome in cancer development and therapy
Bhatt, A. P., Redinbo, M. R., & Bultman, S. J. (2017) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21398 · Cited by 653 · see citing works
Microbiome and Anticancer Immunosurveillance
Zitvogel, L., Ayyoub, M., Routy, B., & Kroemer, G. (2016) · Cell · doi:10.1016/j.cell.2016.03.001 · Cited by 478 · see citing works
γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer
Silva‐Santos, B., Mensurado, S., & Coffelt, S. B. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0153-5 · Cited by 424 · see citing works
γδ T cells: origin and fate, subsets, diseases and immunotherapy
Hu, Y., Hu, Q., Li, Y., Lu, L., Xiang, Z., Yin, Z., Kabelitz, D., & Wu, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01653-8 · Cited by 395 · see citing works
The emerging roles of γδ T cells in cancer immunotherapy
Mensurado, S., Blanco-Domínguez, R., & Silva‐Santos, B. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00722-1 · Cited by 348 · see citing works
Natural and therapy-induced immunosurveillance in breast cancer
Kroemer, G., Senovilla, L., Galluzzi, L., André, F., & Zitvogel, L. (2015) · Nature Medicine · doi:10.1038/nm.3944 · Cited by 308 · see citing works
Dzutsev, A., Badger, J. H., Perez-Chanona, E., Roy, S., Salcedo, R., Smith, C. K., & Trinchieri, G. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052133 · Cited by 302 · see citing works
The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis
Nishida, A., & Andoh, A. (2025) · Cells · doi:10.3390/cells14070488 · Cited by 282 · see citing works
Harnessing innate immune pathways for therapeutic advancement in cancer
Hu, A.-K., Sun, L., Lin, H., Liao, Y., Yang, H., & Mao, Y. Q. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01765-9 · Cited by 265 · see citing works
Targeting galectin-driven regulatory circuits in cancer and fibrosis
Mariño, K. V., Cagnoni, A. J., Croci, D. O., & Rabinovich, G. A. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00636-2 · Cited by 255 · see citing works
Self-citationZhang, Z., Tang, H., Chen, P., Xie, H., & Tao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0074-5 · Cited by 251 · see citing works
Elkrief, A., Derosa, L., Kroemer, G., Zitvogel, L., & Routy, B. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz206 · Cited by 246 · see citing works
The hematopoietic stem cell niche in homeostasis and disease
Calvi, L. M., & Link, D. C. (2015) · Blood · doi:10.1182/blood-2015-07-533588 · Cited by 228 · see citing works
Mohamed, E. T., Sierra, R. A., Trillo-Tinoco, J., Cao, Y. W., Innamarato, P., Payne, K. K., Pulido, Á. D. M., Mandula, J. K., Zhang, S., Thevenot, P., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.03.004 · Cited by 219 · see citing works
Self-citationSvoronos, N., Perales‐Puchalt, A., Allegrezza, M. J., Rutkowski, M. R., Payne, K. K., Tesone, A. J., Nguyen, J. M., Curiel, T. J., Cadungog, M. G., Singhal, S. K., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0502 · Cited by 218 · see citing works
Self-citationAdvancing to the era of cancer immunotherapy
Wang, Y., Wang, M., Wu, H., & Xu, R. (2021) · 癌症：英文版 · doi:10.1002/cac2.12178 · Cited by 219 · see citing works
Toll-like receptor stimulation in cancer: A pro- and anti-tumor double-edged sword
Dajon, M., Iribarren, K., & Cremer, I. (2016) · Immunobiology · doi:10.1016/j.imbio.2016.06.009 · Cited by 211 · see citing works
Microbiota in Tumors: From Understanding to Application
Xie, Y., Xie, F., Zhou, X., Zhang, L., Yang, B., Huang, J., Wang, F., Yan, H., Zhang, L., Zhang, L., et al. (2022) · Advanced Science · doi:10.1002/advs.202200470 · Cited by 211 · see citing works
Calcinotto, A., Brevi, A., Chesi, M., Ferrarese, R., Garcia Perez, L., Grioni, M., Kumar, S., Garbitt, V. M., Sharik, M. E., Henderson, K. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07305-8 · Cited by 223 · see citing works
Exosomes miR-126a released from MDSC induced by DOX treatment promotes lung metastasis
Deng, Z., Rong, Y., Teng, Y., Zhuang, X., Samykutty, A. K., Mu, J., Zhang, L., Cao, P., Yan, J., Miller, D. M., et al. (2016) · Oncogene · doi:10.1038/onc.2016.229 · Cited by 209 · see citing works
Rosean, C. B., Bostic, R. R., Ferey, J. C. M., Feng, T.-Y., Azar, F. N., Tung, K. S. K., Dozmorov, M. G., Smirnova, E., Bos, P. D., & Rutkowski, M. R. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3464 · Cited by 199 · see citing works
Self-citationBiswas, S., Mandal, G., Chowdhury, S. R., Purohit, S., Payne, K. K., Anadon, C. M., Gupta, A., Swanson, P., Yu, X., Conejo-Garcia, J. R., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900692 · Cited by 195 · see citing works
Self-citationChaurio, R. A., Anadon, C. M., Costich, T. L., Payne, K. K., Biswas, S., Harro, C. M., Segura, C. M., Ortiz, A. C., Cortina, C., Rigolizzo, K. E., et al. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.007 · Cited by 194 · see citing works
Self-citationPrebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth
Li, Y., Elmén, L., Segota, I., Xian, Y., Tinoco, R., Feng, Y., Fujita, Y., Segura Muñoz, R. R., Schmaltz, R., Bradley, L. M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.035 · Cited by 189 · see citing works
Function of γδ T cells in tumor immunology and their application to cancer therapy
Park, J. H., & Lee, H. K. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00576-0 · Cited by 191 · see citing works
Sweetening the hallmarks of cancer: Galectins as multifunctional mediators of tumor progression
Girotti, M. R., Salatino, M., Dalotto‐Moreno, T., & Rabinovich, G. A. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20182041 · Cited by 187 · see citing works
Self-citationGalectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation
Sundblad, V., Morosi, L. G., Geffner, J. R., & Rabinovich, G. A. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1701172 · Cited by 185 · see citing works
Self-citationNew Insights Into the Cancer–Microbiome–Immune Axis: Decrypting a Decade of Discoveries
Jain, T., Sharma, P., Are, A. C., Vickers, S. M., & Dudeja, V. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.622064 · Cited by 184 · see citing works
Anadon, C. M., Yu, X., Hänggi, K., Biswas, S., Chaurio, R. A., Martin, A., Payne, K. K., Mandal, G., Innamarato, P., Harro, C. M., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.03.008 · Cited by 174 · see citing works
Self-citationIntestinal microbiota influences clinical outcome and side effects of early breast cancer treatment
Terrisse, S., Derosa, L., Iebba, V., Ghiringhelli, F., Vaz-Luis, I., Kroemer, G., Fidelle, M., Christodoulidis, S., Segata, N., Thomas, A. M., et al. (2021) · Cell Death & Differentiation · doi:10.1038/s41418-021-00784-1 · Cited by 172 · see citing works
The Role of Chronic Inflammation in the Development of Breast Cancer
Danforth, D. N. (2021) · Cancers · doi:10.3390/cancers13153918 · Cited by 173 · see citing works
BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells
Payne, K. K., Mine, J. A., Biswas, S., Chaurio, R. A., Perales‐Puchalt, A., Anadon, C. M., Costich, T. L., Harro, C. M., Walrath, J., Ming, Q., et al. (2020) · Science · doi:10.1126/science.aay2767 · Cited by 162 · see citing works
Self-citationTargeting galectin-1 inhibits pancreatic cancer progression by modulating tumor–stroma crosstalk
Orozco, C. A., Martínez‐Bosch, N., Guerrero, P. E., Vinaixa, J., Dalotto‐Moreno, T., Iglesias, M., Moreno, M., Djurec, M., Poirier, F., Gabius, H., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1722434115 · Cited by 158 · see citing works
Self-citationGalectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis
Méndez‐Huergo, S. P., Blidner, A. G., & Rabinovich, G. A. (2017) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.12.003 · Cited by 153 · see citing works
Self-citationBeneficial bacteria inhibit cachexia
Varian, B. J., Goureshetti, S., Poutahidis, T., Lakritz, J. R., Levkovich, T., Kwok, C., Teliousis, K., Ibrahim, Y. M., Mirabal, S., & Erdman, S. E. (2016) · Oncotarget · doi:10.18632/oncotarget.7730 · Cited by 146 · see citing works
Sipos, A., Ujlaki, G., Mikó, E., Maka, E., Szabó, J., Uray, K., Krasznai, Z. T., & Bai, P. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00295-2 · Cited by 150 · see citing works
The biodiversity Composition of Microbiome in Ovarian Carcinoma Patients
Zhou, B. O., Sun, C., Huang, J. M., Xia, M., Guo, E., Li, N., Lü, H., Shan, W., Wu, Y., Li, Y., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-38031-2 · Cited by 145 · see citing works
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
Thomas, A. M., Fidelle, M., Routy, B., Kroemer, G., Wargo, J. A., Segata, N., & Zitvogel, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00785-8 · Cited by 141 · see citing works
Apoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor metastases in bone
Roca, H., Jones, J., Purica, M. C., Weidner, S., Koh, A. J., Kuo, R., Wilkinson, J. E., Wang, Y., Daignault‐Newton, S., Pienta, K. J., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92466 · Cited by 141 · see citing works
Yang, J., Tan, Q., Fu, Q., Zhou, Y., Hu, Y., Tang, S., Zhou, Y., Zhang, J., Qiu, J., & Lv, Q. (2016) · Breast Cancer · doi:10.1007/s12282-016-0734-z · Cited by 142 · see citing works
Context-dependent functions of pattern recognition receptors in cancer
Man, S. M., & Jenkins, B. J. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00462-5 · Cited by 135 · see citing works
Zhu, Z., Cai, J., Hou, W., Xu, K., Wu, X., Song, Y., Bai, C., Mo, Y., & Zhang, Z. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2166700 · Cited by 134 · see citing works
Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis
Muliaditan, T., Caron, J., Okesola, M., Opzoomer, J. W., Kosti, P., Georgouli, M., Gordon, P., Lall, S. K., Kuzeva, D. M., Pedro, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05346-7 · Cited by 133 · see citing works
Trial Watch: Immunostimulation with Toll-like receptor agonists in cancer therapy
Iribarren, K., Bloy, N., Buqué, A., Cremer, I., Eggermont, A. M. M., Fridman, W. H., Fucikova, J. P., Galon, J., Špíšek, R., Zitvogel, L., et al. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1088631 · Cited by 131 · see citing works
Miller, K. D., O’Connor, S., Pniewski, K. A., Kannan, T., Acosta, R., Mirji, G., Papp, S. B., Hulse, M., Mukha, D., Hlavaty, S. I., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00636-6 · Cited by 132 · see citing works
Microbiome in cancer: Role in carcinogenesis and impact in therapeutic strategies
Rahman, M. M., Islam, M. R., Shohag, S., Ahasan, M. T., Sarkar, N., Khan, H., Hasan, A. M., Cavalu, S. D., & Rauf, A. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112898 · Cited by 129 · see citing works
Engineering the pre-metastatic niche
Aguado, B. A., Bushnell, G. G., Rao, S. S., Jeruss, J. S., & Shea, L. D. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0077 · Cited by 125 · see citing works
Breast and gut microbiome in health and cancer
Zhang, J., Xia, Y., & Sun, J. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.08.002 · Cited by 130 · see citing works
Kimura, Y., Inoue, A., Hangai, S., Saijo, S., Negishi, H., Nishio, J., Yamasaki, S., Iwakura, Y., Yanai, H., & Taniguchi, T. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617903113 · Cited by 121 · see citing works
Translating the ‘Sugar Code’ into Immune and Vascular Signaling Programs
Cerliani, J. P., Blidner, A. G., Toscano, M. A., Croci, D. O., & Rabinovich, G. A. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.11.003 · Cited by 119 · see citing works
Self-citationGut microbiota-mediated immunomodulation in tumor
Liu, X., Chen, Y., Zhang, S., & Dong, L. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01983-x · Cited by 112 · see citing works
Perales‐Puchalt, A., Svoronos, N., Rutkowski, M. R., Allegrezza, M. J., Tesone, A. J., Payne, K. K., Wickramasinghe, J. M., Nguyen, J. M., O’Brien, S. W., Gumireddy, K., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0492 · Cited by 110 · see citing works
Self-citationSatb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells
Tesone, A. J., Rutkowski, M. R., Brencicova, E., Svoronos, N., Perales‐Puchalt, A., Stephen, T. L., Allegrezza, M. J., Payne, K. K., Nguyen, J. M., Wickramasinghe, J. M., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.056 · Cited by 108 · see citing works
Self-citationClinical applications of gut microbiota in cancer biology
Wong, S. H., Kwong, T. N. Y., Wu, C., & Yu, J. Q. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.05.003 · Cited by 100 · see citing works
Eggold, J. T., Chow, S. K.-Y., Melemenidis, S., Wang, J., Natarajan, S., Loo, P. E., Manjappa, R., Viswanathan, V., Kidd, E. A., Engleman, E. G., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-0358 · Cited by 102 · see citing works
Xu, H., Cao, C., Ren, Y., Weng, S., Liu, L., Guo, C., Wang, L., Han, X., Ren, J., & Liu, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.949490 · Cited by 105 · see citing works
Brackett, C. M., Kojouharov, B., Veith, J. M., Greene, K. F., Burdelya, L. G., Gollnick, S. O., Abrams, S. I., & Gudkov, A. V. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521359113 · Cited by 100 · see citing works
Targeting ACSS2 with a Transition-State Mimetic Inhibits Triple-Negative Breast Cancer Growth
Miller, K. D., Pniewski, K. A., Perry, C. E., Papp, S. B., Shaffer, J. D., Velasco‐Silva, J. N., Casciano, J. C., Aramburu, T. M., Srikanth, Y. V. V., Cassel, J. A., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-1847 · Cited by 101 · see citing works
Microbiota—myeloid cell crosstalk beyond the gut
Gorjifard, S., & Goldszmid, R. S. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ri0516-222r · Cited by 97 · see citing works
γδ T Cells: Unexpected Regulators of Cancer Development and Progression
Fleming, C., Morrissey, S. M., Cai, Y., & Yan, J. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.06.003 · Cited by 97 · see citing works
Li, T., Liu, T., Zhu, W., Xie, S., Zhao, Z., Feng, B., Guo, H., & Yang, R. (2021) · Clinical Medicine Insights Oncology · doi:10.1177/11795549211035540 · Cited by 94 · see citing works
Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives
Toubai, T., Mathewson, N. D., Magenau, J. M., & Reddy, P. R. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00539 · Cited by 94 · see citing works
The impact of the intestinal microbiota in therapeutic responses against cancer
Goubet, A., Daillère, R., Routy, B., Derosa, L., Roberti, P. M., & Zitvogel, L. (2018) · Comptes Rendus Biologies · doi:10.1016/j.crvi.2018.03.004 · Cited by 93 · see citing works
The role of microbiota in cancer therapy
Peréz-Chanona, E., & Trinchieri, G. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.01.003 · Cited by 91 · see citing works
Melanoma and microbiota: Current understanding and future directions
Routy, B., Jackson, T., Mählmann, L., Baumgartner, C. K., Blaser, M., Byrd, A., Corvaia, N., Couts, K., Davar, D., Derosa, L., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2023.12.003 · Cited by 89 · see citing works
Shaping the Immune Landscape in Cancer by Galectin-Driven Regulatory Pathways
Rabinovich, G. A., & Conejo-Garcia, J. R. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.03.021 · Cited by 89 · see citing works
Self-citationRecent progress in the development of Toll-like receptor (TLR) antagonists
Patra, M. C., & Choi, S. (2016) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2016.1185415 · Cited by 91 · see citing works
Toll-like receptor-induced cytokines as immunotherapeutic targets in cancers and autoimmune diseases
Patra, M. C., Shah, M., & Choi, S. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.05.002 · Cited by 84 · see citing works
Tumor and Host Factors Controlling Antitumor Immunity and Efficacy of Cancer Immunotherapy
Spranger, S., Sivan, A., Corrales, L. P., & Gajewski, T. F. (2016) · Advances in immunology · doi:10.1016/bs.ai.2015.12.003 · Cited by 86 · see citing works
Yao, Y., Chen, S., Cao, M., Fan, X., Yang, T., Huang, Y., Song, X., Li, Y., Ye, L., Shen, N., et al. (2017) · Nature Communications · doi:10.1038/ncomms15402 · Cited by 86 · see citing works
Microbial Alterations and Risk Factors of Breast Cancer: Connections and Mechanistic Insights
Parida, S., & Sharma, D. (2020) · Cells · doi:10.3390/cells9051091 · Cited by 81 · see citing works
Méndez‐Huergo, S. P., Hockl, P. F., Stupirski, J. C., Maller, S. M., Morosi, L. G., Pinto, N. A., Berón, A. M., Musuruana, J. L., Nasswetter, G. G., Cavallasca, J. A., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03057 · Cited by 82 · see citing works
Self-citationAdvances in glycosylation-mediated cancer-targeted drug delivery
Cai, L., Gu, Z., Zhong, J., Wen, D., Chen, G., Lin, H., Wu, J., & Gu, Z. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.02.009 · Cited by 78 · see citing works
Ding, G., Gong, Q., Ma, J., Liu, X., Wang, Y., & Cheng, X. (2021) · Cancer Science · doi:10.1111/cas.15078 · Cited by 76 · see citing works
Regulatory functions of γδ T cells
Peters, C., Kabelitz, D., & Wesch, D. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2788-x · Cited by 80 · see citing works
Gut Microbiota and Gynecological Cancers: A Summary of Pathogenetic Mechanisms and Future Directions
Borella, F., Carosso, A. R., Cosma, S. D., Preti, M., Collemi, G., Cassoni, P., Bertero, L., & Benedetto, C. (2021) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.0c00839 · Cited by 77 · see citing works
Jiang, T., Chen, L., Huang, Y., Wang, J., Xu, M., Zhou, S., Gu, X. Q., Chen, Y., Liang, K., Pei, Y., et al. (2019) · Nano Letters · doi:10.1021/acs.nanolett.9b00495 · Cited by 70 · see citing works
Role of the microbiome in non-gastrointestinal cancers
Pevsner‐Fischer, M., Tuganbaev, T., Meijer, M. T., Zhang, S., Zeng, Z., Chen, M., & Elinav, E. (2016) · World Journal of Clinical Oncology · doi:10.5306/wjco.v7.i2.200 · Cited by 69 · see citing works
Breast Cancer Immunotherapy: An Update
Makhoul, I., Atiq, M. O., Alwbari, A. M., & Kieber‐Emmons, T. (2018) · Breast Cancer Basic and Clinical Research · doi:10.1177/1178223418774802 · Cited by 72 · see citing works
Porta, C., Sica, A., & Riboldi, E. (2017) · FEBS Journal · doi:10.1111/febs.14288 · Cited by 69 · see citing works
Carpenter, R., Kwak, J., Peyton, S. R., & Lee, J. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0307-x · Cited by 68 · see citing works
Elola, M. T., Ferragut, F., Méndez‐Huergo, S. P., Croci, D. O., Bracalente, C., & Rabinovich, G. A. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.03.008 · Cited by 67 · see citing works
Self-citationImpact of Galectins in Resistance to Anticancer Therapies
Navarro, P., Martínez‐Bosch, N., Blidner, A. G., & Rabinovich, G. A. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3870 · Cited by 64 · see citing works
Self-citationAllegrezza, M. J., Rutkowski, M. R., Stephen, T. L., Svoronos, N., Perales‐Puchalt, A., Nguyen, J. M., Payne, K. K., Singhal, S. K., Eruslanov, E. B., Tchou, J. C., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-1308 · Cited by 63 · see citing works
Self-citationGut Microbiota in Lung Cancer: Where Do We Stand?
Georgiou, K. E., Marinov, B. I., Farooqı, A. A., & Gazouli, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910429 · Cited by 60 · see citing works
PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A–producing γδ T cells
Edwards, S. C., Hedley, A., Hoevenaar, W. H. M., Wiesheu, R., Glauner, T. A., Kilbey, A., Shaw, R., Boufea, K., Batada, N. N., Hatano, S., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211431 · Cited by 57 · see citing works
Microbiota-Propelled T Helper 17 Cells in Inflammatory Diseases and Cancer
Bellone, M., Brevi, A., & Huber, S. (2020) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00064-19 · Cited by 59 · see citing works
Significance of human microbiome in breast cancer: Tale of an invisible and an invincible
Chadha, J., Nandi, D., Atri, Y., & Nag, A. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.07.010 · Cited by 60 · see citing works
Re‐wiring regulatory cell networks in immunity by galectin–glycan interactions
Blidner, A. G., Méndez‐Huergo, S. P., Cagnoni, A. J., & Rabinovich, G. A. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.08.037 · Cited by 57 · see citing works
Self-citationState-of-the-art of regulatory dendritic cells in cancer
Conejo-Garcia, J. R., Rutkowski, M. R., & Cubillos‐Ruiz, J. R. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.003 · Cited by 57 · see citing works
Self-citationMiR‐150 alleviates neuropathic pain via inhibiting toll‐like receptor 5
Ji, L., Shi, J., Lu, J., & Huang, Q. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26269 · Cited by 58 · see citing works
Rutkowski, M. R., Svoronos, N., Perales‐Puchalt, A., & Conejo-Garcia, J. R. (2015) · Advances in cancer research · doi:10.1016/bs.acr.2015.04.011 · Cited by 56 · see citing works
Self-citation
- Authors
- Rutkowski, M. R., Stephen, T. L., Svoronos, N., Allegrezza, M. J., Tesone, A. J., Perales-Puchalt, A., Brencicova, E., Escovar-Fadul, X., Nguyen, J. M., Cadungog, M. G., Zhang, R., Salatino, M., Tchou, J., Rabinovich, G. A., & Conejo-Garcia, J. R.
- Affiliations
- The Wistar Institute (US)
- Christiana Care Health System (US)
- University of Pennsylvania (US)
- Abramson Cancer Center (US)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Conejo-Garcia, Jose R.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 27
- Issue
- 1
- Pages
- 27-40
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4293269
- OpenAlex
- W2164918734
- Cited by
- 311
- References
- 28
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 24 · 2023: 30 · 2022: 27 · 2021: 34 · 2020: 22 · 2019: 19 · 2018: 27 · 2017: 35 · 2016: 35 · 2015: 16
- FWCI
- 13.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Conicet (submittedVersion, cc-by-nc-sa)
- Funders
- National Cancer Institute (CA010815, R01CA157664, U54CA151662, R01CA178687, R01CA163377, R01CA124515, T32CA009171, P30CA010815)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- TLR5, flagellin, commensal bacteria, tumor-promoting inflammation, myeloid-derived suppressor cells, granulocytic MDSCs, γδ T cells, galectin-1, interleukin-6, IL-17, antitumor immunity, malignant progression, ovarian cancer, breast cancer, microbiome
- MeSH terms
- Animals, Cells, Cultured, Humans, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Neoplasm Transplantation, Neoplasms, Signal Transduction, Interleukin-6, Gene Expression Regulation, Neoplastic, Interleukin-17, Polymorphism, Single Nucleotide, Galectin 1, Cell Line, Tumor, Toll-Like Receptor 5, Mice, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
